The proposed research is an extension of ongoing studies on the growth and development of neuronal populations derived from the neural crest. Using a combination of immunocytochemical, biochemical and pharmacologic techniques, we have defined factors governing phenotypic expression in sympathetic neuroblasts, the factors regulating embryogenesis of the sympathetic system, and the role of nerve growth factor. In parallel studies we have begun to define the factors governing the biochemical development of peripheral sensory neurons. The present studies will focus on the molecular mechanisms regulating development of the putative neurotransmitters substance P (SP) and somatostatin (SS) in peripheral sensory neurons. More specifically, we hope to a) define the utility of SP as a biochemical marker for peripheral sensory neurons, b) further characterize the reciprocal interactions between sensory neurons and their fields of innervation, c) characterize the role of nerve growth factor in sensory neuron development, d) define the role of the central nervous system in regulating growth of peripheral sensory neurons, e) characterize the role of SP in peripheral nociceptive pathways, f) use the above information to understand processes governing neuronal phenotypic expression and interneuronal communication. It is hoped that these studies will elucidate mechanisms leading to abnormal neuronal development and indicate new therapeutic approaches to diseases of disordered neural development.